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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 73 records · Page 4Linked to original sources

Pregnancy-induced changes in substance P and neurokinin 1 receptor (NK1-R) expression in the rat uterus.

Adrenergic nerve fibres of the mammalian uterus degenerate during pregnancy. The behaviour of peptidergic fibres, such as substance P-positive fibres and of its preferred neurokinin 1 receptor (NK1-R), is poorly studied in the pregnant rat uterus. The present study analysed the changes in substance P immunoreactivity and in the expression of NK1-R protein in the uterus of non-pregnant, pregnant (days 7, 14 and 21) and postpartum rats (days 1, 8 and 22) by immunohistology, dot blot analysis and western blot analysis. In non-pregnant rats, substance P-positive fibres were localized to the myometrium; these fibres progressively disappeared during gestation and were almost absent at term (day 21). At day 22 post partum, substance P-positive fibres had recovered to numbers comparable with those in the non-pregnant uterus. Dot blot analysis revealed a significant decrease in the immunoreactivity of substance P in the uterus at mid-pregnancy (day 14) and especially at term. Expression of the NK1-R protein showed a progressive increase throughout pregnancy reaching a peak on day 1 post partum; downregulation of NK1-R protein occurred on day 8 post partum. The low and high expressions of NK1-R protein were coincident with a large number of eosinophils and almost no eosinophils in the uterus at oestrus and at term, respectively. It was concluded that substance P immunoreactivity is inversely correlated with NK1-R protein expression in the pregnant and postpartum uterus. The marked upregulation of NK1-R protein at term and after birth indicates that the NK1-R may be involved in the complex regulation of labour and postpartum physiology. However, it is likely that the NK1-protein is not involved in the recruitment of eosinophils into the uterus at oestrus.

Animals↗

Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c. 147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.

Alleles↗

A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy.

INTRODUCTION: Renal cell carcinoma (RCC) has a poor prognosis when metastasized to distant sites, although immunotherapy may offer a prolongation of survival in selected patient groups. Unfortunately, no treatment options remain when immunotherapy fails. In this phase IIa trial the tolerability and efficacy of the antifolate drug methotrexate-human serum albumin (MTX-HSA) were evaluated in patients with metastatic RCC who progressed after first-line immunotherapy. PATIENTS AND METHODS: A total of 17 patients started treatment, and 14 (12 men, 2 women) were evaluable for response according to the phase IIa Gehan design. Patients had had prior tumor nephrectomy, were in relatively good general condition, had no impairment of renal, liver or bone marrow function, and had progressive metastatic disease after treatment with interferon-alpha (IFN-alpha) with or without cis-retinoic acid (EORTC protocols 30951 and 30947). MTX-HSA was given once a week intravenously on an outpatient basis at a dose of 50 mg/m(2). The treatment interval was prolonged in those patients who had not yet recovered from previous toxicities. RESULTS: Toxicity was manageable, relatively mild to moderate and reversible in most cases. Grade 2/3 mucositis (10/17) and grade 3 elevated transaminase levels (4/17) were most frequent, and in only one patient was a grade 4 thrombocytopenia reported. Of three inevaluable patients, one discontinued treatment due to drug-related toxicities. The mean administration interval was 12.1 days, and 7 of 14 evaluable patients had treatment intervals of 1 or 2 weeks. No objective responses were seen, although eight patients had stable disease (stabilization >2 months) for up to 8 months (median 121 days). CONCLUSION: MTX-HSA was generally well tolerated and can be given on an outpatient basis, but no objective responses were seen in patients with metastatic RCC who had progressed after previous immunotherapy.

Adult↗

[A concept for the assessment of quality of life in patients with carcinomas of the upper aerodigestive tract].

BACKGROUND: The quality of life (QoL) of patients with malignant diseases decreases significantly. OBJECTIVE: The evaluation of QoL is generally not part of the management of patients with head and neck cancer. The aim of this study was to develop an additional disease- and treatment-specific questionnaire to evaluate QoL in surgically treated head and neck cancer patients. PATIENTS AND METHODS: The general QoL was evaluated with the QLQ-C30 questionnaire developed by the European Organisation of Research and Treatment of Cancer (EORTC). RESULTS: The disease-specific QoL was evaluated using the EORTC H&N35 module. The new questionnaire "Kiel Head and Neck 17" (KQL H&N-17) is a disease- and treatment-specific addition especially in regard to side effects caused by surgical treatment. CONCLUSIONS: A wide application of this whole concept is needed to obtain comparable results from studies suitable for evaluating QoL in patients receiving different treatments for their malignant diseases. Moreover, the effectiveness and quality of treatment could be controlled better, which would help to increase the QoL of these patients.

Activities of Daily Living↗

[Outpatient treatment of acute deep venous thrombosis of the lower limbs].

The outpatient management of acute deep vein thrombosis could replace the inpatient care for most patients. Fixed-dose, weight-adjusted low-molecular-weight heparins, as efficacious and safe as unfractionated heparin, allow home treatment for selected and eligible patients. The main exclusion criteria are severe renal insufficiency, high risk of bleeding, pulmonary embolism with unstable hemodynamics, allergy to heparin and suspected non-compliance. Programs for outpatient management need, after appropriate selection, adequate patient education, easy access to health-care professionals and daily follow-up during heparin treatment.

Acute Disease↗

Myocardial ischaemia in patients with impaired left ventricular function undergoing coronary artery bypass grafting--milrinone versus nifedipin.

BACKGROUND AND OBJECTIVE: Myocardial ischaemia and infarction are major complications immediately after coronary artery bypass grafting. They may be due to incomplete surgical revascularization, perioperative anaesthetic management or vasospasm of arterial grafts, e.g. the internal mammary artery. Infusions of nifedipine or milrinone have been advocated to prevent spasm of the mammary artery. The study compared the incidence of myocardial ischaemia after continuous infusion of either nifedipine (0.2 microg kg(-1) min(-1)) or milrinone (0.375 microg kg(-1) min(-1)) in patients with compromised left ventricular function scheduled for elective coronary artery bypass graft. METHODS: After Institutional Review Board approval, this double-blinded randomized clinical study enrolled 30 adult patients with compromised left ventricular function (ejection fraction < 0.4) scheduled for elective coronary artery bypass grafting after written informed consent had been obtained. Ischaemia was detected by Holter electrocardiographic monitoring. The incidence of myocardial cell death was monitored by serial determinations of the creatine kinase-MB (CK-MB) and troponin-I. RESULTS: New ST elevation > or = 0.2 mV or new ST depression < or = 0.1 mV occurred in five of 15 patients in the milrinone group (33.3%) and in 13 of 15 patients (86.6%) in the nifedipine group (P < 0.05). There were increases in CK-MB and troponin-I in both groups. Twenty-four hours postoperatively, CK-MB (P = 0.003) and troponin-I (P = 0.001) were significantly higher in the nifedipine group. CONCLUSIONS: Perioperative continuous infusion of milrinone, compared with nifedipine, results in a significantly lower incidence of myocardial ischaemia and myocardial cell damage after elective coronary artery bypass grafting.

Aged↗

Coexistence of non-Hodgkin's lymphoma and non-small cell lung carcinoma: diagnosis and treatment.

Abstract. In this communication, we will present a very rare case of the coexistence of non-Hodgkin's lymphoma (NHL; low malignant lymphocytic lymphoma of the B-cell type) and a non-small-cell lung carcinoma (NSCLC). A patient with a 15-year history of NHL developed a generalized relapse of the lymphoma with an additional tumor mass in the left lower lobe of the lung. Bronchoscopy showed the evidence of the NHL. Due to non-responding chemotherapy on the lung tumor, the coexistence of a second malignancy was histologically proved in a second bronchoscopy. Resection of the lung tumor with complex lobectomy and lymphadenectomy was performed. After that, chemotherapy with four cycles of carboplatin supplemented with taxol was induced. The patient was discharged from the hospital with a stable remission of both tumor diseases. Restaging after six months showed no evidence of a tumor relapse. This is a very rare case of the coexistence of NHL and NSCLC; we will discuss the difficulty of diagnostic and treatment of both tumor diseases.

Aged↗

Left ventricular assist stand-by for high-risk cardiac surgery.

BACKGROUND: Patients with severely impaired left-ventricular pump function who are eligible for heart transplantation increasingly undergo high-risk cardiac surgery due to the scarcity of donor organs. If these patients also qualify for long-term mechanical support, the latter can be used as back-up in case of postcardiotomy failure. METHODS: Since 1994, 36 patients (34 male, 2 female; mean age 51 +/- 7 years) underwent coronary bypass surgery/aneurysmectomy (n = 27), aortic valve replacement (n = 4), both (n = 1), or partial left ventriculectomy (n = 4) with a long-term mechanical assist device (Novacor, HeartMate, DeBakey) and were kept on stand-by with the device. Average left ventricular ejection fraction was 23 +/- 9 %, NYHA 2.9 +/- 0.5, and CCS 2.7 +/- 0.9. An intraaortic balloon pump was inserted prior to surgery in 13 patients. RESULTS: In 31 patients, high-risk surgery was performed, whereas 5 patients underwent immediate device placement as coronary revascularization was deemed impossible. 6 patients had postcardiotomy failure after coronary bypass surgery and were immediately provided with a long-term assist system. There were no significant differences in risk factors between the patient subsets. All conservatively operated patients survived and left the institution after 9.4 days and are currently at NYHA 1.5 +/- 0.5 or CCS 1.0 +/- 0, respectively. 6 of the 11 LVAD patients could be bridged to heart transplantation after 43 - 418 days, and 1 patient is still on support. CONCLUSION: High-risk conventional surgery with LVAD stand-by is feasible and seems to be a valuable alternative for heart-transplant candidates.

Female↗

Mitral valve surgery in patients with poor left ventricular function.

BACKGROUND: Mitral valve surgery for the correction of secondary mitral valve regurgitation (MR) in cardiomyopathy is associated with a poor outcome. Numerous studies have identified a severe left ventricular dysfunction as an indicator for a poor prognosis. The aim of the study was to asses the follow-up after mitral valve surgery and severe left ventricular dysfunction. METHODS: Between 1994 and 2000, 31 patients with mitral regurgitation and a left ventricular ejection fraction of below thirty percent undergoing isolated repair (n = 16) or replacement (n = 15) were investigated. All patients received maximal drug therapy. Twenty-one patients were New York Heart Association (NYHA) class III and 10 were class IV. Follow-up with echocardiography, ECG, and chest x-ray was performed in 87 % of the survivors. The mean duration of follow-up was 39 +/- 16 months. RESULTS: The mean duration of ICU and hospital stay was 3.6 +/- 2.1 days and 8.1 +/- 5.4 days, respectively. The 1-, 2-, and 5-year survival rates were 91 %, 84 %, and 77 %, respectively. NYHA class improved from 3.3 +/- 0.8 to 2.1 +/- 0.7 at follow-up (p < 0.01). The ejection fraction improved from 23.1 +/- 6.6 % to 36 +/- 6.8 % at follow-up (p < 0.02). Freedom from readmission for heart failure was 85 %, 79 %, and 68 % at 1-, 2-, and 5 years, respectively. CONCLUSIONS: Mitral valve surgery improves left ventricular function and reduces heart failure severity in patients with MR and cardiomyopathy. High-risk mitral valve surgery may be an alternative to heart transplantation in selected patients.

Atrial Fibrillation↗

Congenital myasthenic syndrome (CMS) in three European kinships due to a novel splice mutation (IVS7 - 2 A/G) in the epsilon acetylcholine receptor (AChR) subunit gene.

Mutations in the epsilon-acetylcholine receptor (AChR epsilon) subunit gene cause congenital myasthenic syndromes (CMS) with postsynaptic neural transmission defects. We present 3 male and 2 female patients from three unrelated Croatian, Hungarian, and Russian families with autosomal recessive CMS. All patients manifested with variable degrees of ophthalmoparesis and generalized, fatiguable muscle weakness since birth or early infancy. Electrophysiological studies showed a decremental response in all patients indicating a neuromuscular transmission defect. Pyridostigmine treatment improved the proximal muscle weakness whereas the ophthalmoparesis remained unchanged in all patients. Analysis of the AChR epsilon subunit gene showed homozygosity for a novel splice site mutation of intron 7 epsilon(IVS7-2A/G) in the two Croatian siblings. epsilon-mRNA analysis by RT-PCR and direct sequencing revealed that exon 7 was spliced directly to exon 9 with skipping of exon 8. The Hungarian and Russian patients were heteroallelic carriers of the same mutation epsilon(IVS7-2A/G) and of a frameshifting mutation epsilon 70insG and epsilon 1293insG, respectively. We hypothesize that altered splice products may not be expressed as functional receptors at the cell surface. A haplotype analysis with polymorphic markers revealed a high degree of similarity for the epsilon(IVS7-2A/G) carrying allele in all families and may therefore indicate a common origin of the mutation.

Adolescent↗

Risk factors for methicillin-resistant Staphylococcus aureus carriage in residents of German nursing homes.

OBJECTIVES: To determine the prevalence of and the risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage in nursing home residents in the Rhine-Neckar region of southern Germany. DESIGN: Point-prevalence survey. SETTING: Forty-seven nursing homes in the region. PARTICIPANTS: All residents of the approached nursing homes who agreed to participate. METHODS: After informed consent was obtained, all participants had their nares swabbed, some personal data collected, or both. All swabs were examined for growth of MRSA. All S. aureus isolates underwent oxacillin susceptibility testing and polymerase chain reaction for demonstration of the mecA gene. All MRSA isolates were typed using pulsed-field gel electrophoresis after digestion with SmaI. RESULTS: Swabs from 3,236 nursing home residents yielded 36 MRSA strains, contributing to a prevalence rate of 1.1%. Significant risk factors for MRSA carriage in the multivariate analysis were the presence of wounds or urinary catheters, limited mobility, admission to a hospital during the preceding 3 months, or stay in a medium-size nursing home. One predominant MRSA strain could be detected in 30 of the 36 MRSA carriers. CONCLUSIONS: The prevalence of MRSA in German nursing homes is still low. These residents seemed to acquire their MRSA in the hospital and transfer it to their nursing home. Apart from well-known risk factors for the acquisition of MRSA, we identified the size of the nursing home as an independent risk factor. This might be due to an increased use of and microbials in nursing homes of a certain size.

Aged↗

Optimizing fluid therapy in mechanically ventilated patients after cardiac surgery by on-line monitoring of left ventricular stroke volume variations. Comparison with aortic systolic pressure variations.

BACKGROUND: Mechanical ventilation causes changes in left ventricular preload leading to distinct variations in left ventricular stroke volume and systolic arterial pressure. Retrospective off-line quantification of systolic arterial pressure variations (SPV) has been validated as a sensitive method of predicting left ventricular response to volume administration. We report the real-time measurement of left ventricular stroke volume variations (SVV) by continuous arterial pulse contour analysis and compare it with off-line measurements of SPV in patients after cardiac surgery. METHODS: SVV and SPV were determined before and after volume loading with colloids in 20 mechanically ventilated patients. RESULTS: SVV and SPV decreased significantly after volume loading and were correlated (r=0.89; P<0.001). Changes in SVV and changes in SPV as a result of volume loading were also significantly correlated (r=0.85; P<0.005). Changes in SVV correlated significantly with changes in stroke volume index (SVI) (r=0.67; P<0.005) as did changes in SPV (r=0.56; P<0.05). SVV determined before volume loading correlated significantly with changes in SVI (R=0.67; P <0.005). Using receiver operating characteristics curves, the area under the curve was statistically greater for SVV (0.824; 95% confidence interval: [CI] 0.64-1.0) and SPV (0.81; CI: 0.62-1.0) than for central venous pressure (0.451; CI: 0.17-0.74). CONCLUSIONS: Monitoring of SVV enables real-time prediction and monitoring of the left ventricular response to preload enhancement in patients after cardiac surgery and is helpful for guiding volume therapy.

Aorta, Abdominal↗

Analysis of the genes SLC7A9 and SLC3A1 in unclassified cystinurics: mutation detection rates and association between variants in SLC7A9 and the disease.

Cystinuria is a common inherited disorder of defective renal reabsorption of cystine and dibasic amino acids. Recently, 2 responsible genes have been identified: mutations in the SLC3AI gene encoding the glycoprotein rBAT cause cystinuria type I, while variants in the SLC7A9 gene have been demonstrated in non-type I cystinuria; its gene product b(0)+AT is the light chain of the renal cystine transport system rBAT/b(0),+-AT. To estimate the role of both genes in the etiology of cystinuria, we searched for sequence alterations in SLC7A9 and SLC3AI: 30 unclassified cystinurics were investigated. In 50% of patients (15/30), point mutations in SLC3A1 were detected. Screening of the SLC7A9 gene revealed 10 mutations in 8 patients corresponding to a frequency of 27%. In addition to previously published mutations in the SLC7A9 gene, we detected 2 new mutations (F 140S, c747delG). An overall detection rate of 73% (22/30) in unclassified patients is delineated for mutations in both genes. In 33% (10/30), 2 mutations were detected, in 40% (12/30) 1 mutation. Furthermore, 5 new polymorphic sites were identified in SLC7A9. While the base pair variation in intron 9 is homogeneously distributed in patients and control individuals, the allelic and genotypic distributions of the polymorphisms in 3 exons of SLC7A9--exons 2, 5 and 6--and intron 3 differ significantly between both groups. Our results suggest that some haplotypes defined through the exons 2, 5 and 6 and intron 3 might be markers of a functional variant in the SLC7A9 gene. Evidently, since the mutation detection rates in the 2 so far known cystinuria genes never reach 100%, further genes and modulating factors should influence the phenotype in a subset of patients. However, the presented data show that testing for mutations in the 2 currently known cystinuria genes is already a meaningful approach to the molecular diagnostics of the disease.

Amino Acid Transport Systems, Basic↗